Skip to main content
SpringerLink
Log in

Taste Receptor Gene Expression Outside the Gustatory System

  • Chapter
  • First Online:
Taste and Smell

Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 23))

Abstract

The sense of taste facilitates the recognition of beneficial or potentially harmful food constituents prior to ingestion. For the detection of tastants, epithelial specializations in the oral cavity are equipped with taste receptor molecules that interact with sweet, umami (the taste of l-amino acids), salty, sour, and bitter-tasting substances. Over the past years, numerous tissues in addition to gustatory sensory tissue have been identified to express taste receptor molecules. These findings bear important implications for the roles taste receptors fulfill in vertebrates, which are currently envisioned much broader than thought previously. Taste receptive molecules are present in the brain, respiratory and gastrointestinal tracts, heart, male reproductive tissue, as well as other areas of the body just beginning to emerge. This review summarizes current knowledge on the occurrence and functional implications of taste receptive molecules outside the oral cavity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Behrens M, Meyerhof W (2011) Gustatory and extragustatory functions of mammalian taste receptors. Physiol Behav 105(1):4–13

    Article  CAS  Google Scholar 

  2. Bezencon C, le Coutre J, Damak S (2007) Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells. Chem Senses 32(1):41–49

    Article  CAS  Google Scholar 

  3. Chen MC, Wu SV, Reeve JR Jr, Rozengurt E (2006) Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels. Am J Physiol Cell Physiol 291(4):C726–C739

    Article  CAS  Google Scholar 

  4. Daly K, Al-Rammahi M, Moran A, Marcello M, Ninomiya Y, Shirazi-Beechey SP (2013) Sensing of amino acids by the gut-expressed taste receptor T1R1–T1R3 stimulates CCK secretion. Am J Physiol Gastrointest Liver Physiol 304(3):G271–G282. doi:10.1152/ajpgi.00074.2012

    Article  CAS  Google Scholar 

  5. Dotson CD, Zhang L, Xu H, Shin YK, Vigues S, Ott SH, Elson AE, Choi HJ, Shaw H, Egan JM, Mitchell BD, Li X, Steinle NI, Munger SD (2008) Bitter taste receptors influence glucose homeostasis. PLoS One 3(12):e3974

    Article  CAS  Google Scholar 

  6. Dyer J, Salmon KS, Zibrik L, Shirazi-Beechey SP (2005) Expression of sweet taste receptors of the T1R family in the intestinal tract and enteroendocrine cells. Biochem Soc Trans 33(Pt 1):302–305

    Article  CAS  Google Scholar 

  7. Geraedts MC, Takahashi T, Vigues S, Markwardt ML, Nkobena A, Cockerham RE, Hajnal A, Dotson CD, Rizzo MA, Munger SD (2012) Transformation of postingestive glucose responses after deletion of sweet taste receptor subunits or gastric bypass surgery. Am J Physiol Endocrinol Metab 303(4):E464–E474

    Article  CAS  Google Scholar 

  8. Glendinning JI, Yiin YM, Ackroff K, Sclafani A (2008) Intragastric infusion of denatonium conditions flavor aversions and delays gastric emptying in rodents. Physiol Behav 93(4–5):757–765

    Article  CAS  Google Scholar 

  9. Hao S, Sternini C, Raybould HE (2008) Role of CCK1 and Y2 receptors in activation of hindbrain neurons induced by intragastric administration of bitter taste receptor ligands. Am J Physiol Regul Integr Comp Physiol 294(1):R33–R38

    Article  CAS  Google Scholar 

  10. Hass N, Schwarzenbacher K, Breer H (2010) T1R3 is expressed in brush cells and ghrelin-producing cells of murine stomach. Cell Tissue Res 339(3):493–504

    Article  CAS  Google Scholar 

  11. Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, Kim HH, Xu X, Chan SL, Juhaszova M, Bernier M, Mosinger B, Margolskee RF, Egan JM (2007) Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A 104:15069–15074

    Article  CAS  Google Scholar 

  12. Janssen S, Laermans J, Verhulst PJ, Thijs T, Tack J, Depoortere I (2011) Bitter taste receptors and alpha-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying. Proc Natl Acad Sci U S A 108(5):2094–2099

    Article  CAS  Google Scholar 

  13. Jeon TI, Zhu B, Larson JL, Osborne TF (2008) SREBP-2 regulates gut peptide secretion through intestinal bitter taste receptor signaling in mice. J Clin Invest 118(11):3693–3700

    Article  CAS  Google Scholar 

  14. Kaji I, Karaki S, Fukami Y, Terasaki M, Kuwahara A (2009) Secretory effects of a luminal bitter tastant and expressions of bitter taste receptors, T2Rs, in the human and rat large intestine. Am J Physiol Gastrointest Liver Physiol 296(5):G971–G981

    Article  CAS  Google Scholar 

  15. Kyriazis GA, Soundarapandian MM, Tyrberg B (2012) Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion. Proc Natl Acad Sci U S A 109(8):E524–E532. doi:10.1073/pnas.1115183109

    Article  CAS  Google Scholar 

  16. Mace OJ, Affleck J, Patel N, Kellett GL (2007) Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2. J Physiol 582(Pt 1):379–392

    Article  CAS  Google Scholar 

  17. Margolskee RF, Dyer J, Kokrashvili Z, Salmon KS, Ilegems E, Daly K, Maillet EL, Ninomiya Y, Mosinger B, Shirazi-Beechey SP (2007) T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proc Natl Acad Sci U S A 104(38):15075–15080

    Article  CAS  Google Scholar 

  18. Nakagawa Y, Nagasawa M, Yamada S, Hara A, Mogami H, Nikolaev VO, Lohse MJ, Shigemura N, Ninomiya Y, Kojima I (2009) Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion. PLoS One 4(4):e5106. doi:10.1371/journal.pone.0005106

    Article  CAS  Google Scholar 

  19. Prandi S, Bromke M, Hubner S, Voigt A, Boehm U, Meyerhof W, Behrens M (2013) A subset of mouse colonic goblet cells expresses the bitter taste receptor tas2r131. PLoS One 8(12):e82820. doi:10.1371/journal.pone.0082820

    Article  CAS  Google Scholar 

  20. Rozengurt N, Wu SV, Chen MC, Huang C, Sternini C, Rozengurt E (2006) Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon. Am J Physiol Gastrointest Liver Physiol 291(5):G792–G802

    Article  CAS  Google Scholar 

  21. Shirazi-Beechey SP, Moran AW, Batchelor DJ, Daly K, Al-Rammahi M (2011) Glucose sensing and signalling; regulation of intestinal glucose transport. Proc Nutr Soc 70(2):185–193. doi:10.1017/S0029665111000103

    Article  CAS  Google Scholar 

  22. Steinert RE, Gerspach AC, Gutmann H, Asarian L, Drewe J, Beglinger C (2011) The functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Clin Nutr 30(4):524–532. doi:10.1016/j.clnu.2011.01.007

    Article  CAS  Google Scholar 

  23. Sutherland K, Young RL, Cooper NJ, Horowitz M, Blackshaw LA (2007) Phenotypic characterization of taste cells of the mouse small intestine. Am J Physiol Gastrointest Liver Physiol 292(5):G1420–G1428

    Article  CAS  Google Scholar 

  24. Wu SV, Chen MC, Rozengurt E (2005) Genomic organization, expression, and function of bitter taste receptors (T2R) in mouse and rat. Physiol Genomics 22(2):139–149

    Article  CAS  Google Scholar 

  25. Wu SV, Rozengurt N, Yang M, Young SH, Sinnett-Smith J, Rozengurt E (2002) Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells. Proc Natl Acad Sci U S A 99(4):2392–2397

    Article  CAS  Google Scholar 

  26. Young RL, Sutherland K, Pezos N, Brierley SM, Horowitz M, Rayner CK, Blackshaw LA (2009) Expression of taste molecules in the upper gastrointestinal tract in humans with and without type 2 diabetes. Gut 58(3):337–346

    Article  CAS  Google Scholar 

  27. Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JS, Liggett SB (2010) Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nat Med 16(11):1299–1304

    Article  CAS  Google Scholar 

  28. Finger TE, Bottger B, Hansen A, Anderson KT, Alimohammadi H, Silver WL (2003) Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration. Proc Natl Acad Sci U S A 100(15):8981–8986

    Article  CAS  Google Scholar 

  29. Finger TE, Kinnamon SC (2011) Taste isn’t just for taste buds anymore. F1000 Biol Rep 3:20

    Google Scholar 

  30. Lee RJ, Xiong G, Kofonow JM, Chen B, Lysenko A, Jiang P, Abraham V, Doghramji L, Adappa ND, Palmer JN, Kennedy DW, Beauchamp GK, Doulias PT, Ischiropoulos H, Kreindler JL, Reed DR, Cohen NA (2012) T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection. J Clin Invest 122(11):4145–4159. doi:10.1172/JCI64240

    Article  CAS  Google Scholar 

  31. Orsmark-Pietras C, James A, Konradsen JR, Nordlund B, Soderhall C, Pulkkinen V, Pedroletti C, Daham K, Kupczyk M, Dahlen B, Kere J, Dahlen SE, Hedlin G, Melen E (2013) Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics. Eur Respir J 42(1):65–78. doi:10.1183/09031936.00077712

    Article  CAS  Google Scholar 

  32. Shah AS, Ben-Shahar Y, Moninger TO, Kline JN, Welsh MJ (2009) Motile cilia of human airway epithelia are chemosensory. Science 325(5944):1131–1134

    Article  CAS  Google Scholar 

  33. Tizzano M, Cristofoletti M, Sbarbati A, Finger TE (2011) Expression of taste receptors in solitary chemosensory cells of rodent airways. BMC Pulm Med 11:3. doi:10.1186/1471-2466-11-3

    Article  CAS  Google Scholar 

  34. Tizzano M, Finger TE (2013) Chemosensors in the nose: guardians of the airways. Physiology (Bethesda) 28(1):51–60. doi:10.1152/physiol.00035.2012

    Article  CAS  Google Scholar 

  35. Tizzano M, Gulbransen BD, Vandenbeuch A, Clapp TR, Herman JP, Sibhatu HM, Churchill ME, Silver WL, Kinnamon SC, Finger TE (2010) Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Proc Natl Acad Sci U S A 107(7):3210–3215

    Article  CAS  Google Scholar 

  36. Voigt A, Hubner S, Lossow K, Hermans-Borgmeyer I, Boehm U, Meyerhof W (2012) Genetic labeling of Tas1r1 and Tas2r131 taste receptor cells in mice. Chem Senses 37(9):897–911

    Article  CAS  Google Scholar 

  37. Zhang CH, Lifshitz LM, Uy KF, Ikebe M, Fogarty KE, ZhuGe R (2013) The cellular and molecular basis of bitter tastant-induced bronchodilation. PLoS Biol 11(3):e1001501. doi:10.1371/journal.pbio.1001501

    Article  CAS  Google Scholar 

  38. Iwatsuki K, Nomura M, Shibata A, Ichikawa R, Enciso PL, Wang L, Takayanagi R, Torii K, Uneyama H (2010) Generation and characterization of T1R2-LacZ knock-in mouse. Biochem Biophys Res Commun 402(3):495–499

    Article  CAS  Google Scholar 

  39. Li F (2013) Taste perception: from the tongue to the testis. Mol Hum Reprod 19(6):349–360. doi:10.1093/molehr/gat009

    Article  CAS  Google Scholar 

  40. Li F, Zhou M (2012) Depletion of bitter taste transduction leads to massive spermatid loss in transgenic mice. Mol Hum Reprod 18(6):289–297

    Article  CAS  Google Scholar 

  41. Meyer D, Voigt A, Widmayer P, Borth H, Huebner S, Breit A, Marschall S, de Angelis MH, Boehm U, Meyerhof W, Gudermann T, Boekhoff I (2012) Expression of Tas1 taste receptors in mammalian spermatozoa: functional role of Tas1r1 in regulating basal Ca(2)(+) and cAMP concentrations in spermatozoa. PLoS One 7(2):e32354. doi:10.1371/journal.pone.0032354

    Article  CAS  Google Scholar 

  42. Mosinger B, Redding KM, Parker MR, Yevshayeva V, Yee KK, Dyomina K, Li Y, Margolskee RF (2013) Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility. Proc Natl Acad Sci U S A 110(30):12319–12324. doi:10.1073/pnas.1302827110

    Article  CAS  Google Scholar 

  43. Xu J, Cao J, Iguchi N, Riethmacher D, Huang L (2013) Functional characterization of bitter-taste receptors expressed in mammalian testis. Mol Hum Reprod 19(1):17–28. doi:10.1093/molehr/gas040

    Article  CAS  Google Scholar 

  44. Garcia-Esparcia P, Schluter A, Carmona M, Moreno J, Ansoleaga B, Torrejon-Escribano B, Gustincich S, Pujol A, Ferrer I (2013) Functional genomics reveals dysregulation of cortical olfactory receptors in Parkinson disease: novel putative chemoreceptors in the human brain. J Neuropathol Exp Neurol 72(6):524–539. doi:10.1097/NEN.0b013e318294fd76

    Article  CAS  Google Scholar 

  45. Ansoleaga B, Garcia-Esparcia P, Llorens F, Moreno J, Aso E, Ferrer I (2013) Dysregulation of brain olfactory and taste receptors in AD, PSP and CJD, and AD-related model. Neuroscience 248C:369–382. doi:10.1016/j.neuroscience.2013.06.034

    Article  CAS  Google Scholar 

  46. Cong WN, Wang R, Cai H, Daimon CM, Scheibye-Knudsen M, Bohr VA, Turkin R, Wood WH 3rd, Becker KG, Moaddel R, Maudsley S, Martin B (2013) Long-term artificial sweetener acesulfame potassium treatment alters neurometabolic functions in C57BL/6J mice. PLoS One 8(8):e70257. doi:10.1371/journal.pone.0070257

    Article  CAS  Google Scholar 

  47. Dehkordi O, Rose JE, Fatemi M, Allard JS, Balan KV, Young JK, Fatima S, Millis RM, Jayam-Trouth A (2012) Neuronal expression of bitter taste receptors and downstream signaling molecules in the rat brainstem. Brain Res 1475:1–10. doi:10.1016/j.brainres.2012.07.038

    Article  CAS  Google Scholar 

  48. Ren X, Zhou L, Terwilliger R, Newton SS, de Araujo IE (2009) Sweet taste signaling functions as a hypothalamic glucose sensor. Front Integr Neurosci 3:12

    Article  CAS  Google Scholar 

  49. Singh N, Vrontakis M, Parkinson F, Chelikani P (2011) Functional bitter taste receptors are expressed in brain cells. Biochem Biophys Res Commun 406(1):146–151

    Article  CAS  Google Scholar 

  50. Foster SR, Porrello ER, Purdue B, Chan HW, Voigt A, Frenzel S, Hannan RD, Moritz KM, Simmons DG, Molenaar P, Roura E, Boehm U, Meyerhof W, Thomas WG (2013) Expression, regulation and putative nutrient-sensing function of taste GPCRs in the heart. PLoS One 8(5):e64579. doi:10.1371/journal.pone.0064579

    Article  CAS  Google Scholar 

  51. Fukuda N, Yomogida K, Okabe M, Touhara K (2004) Functional characterization of a mouse testicular olfactory receptor and its role in chemosensing and in regulation of sperm motility. J Cell Sci 117(Pt 24):5835–5845. doi:10.1242/jcs.01507

    Article  CAS  Google Scholar 

  52. Spehr M, Gisselmann G, Poplawski A, Riffell JA, Wetzel CH, Zimmer RK, Hatt H (2003) Identification of a testicular odorant receptor mediating human sperm chemotaxis. Science 299(5615):2054–2058

    Article  CAS  Google Scholar 

  53. Elliott RA, Kapoor S, Tincello DG (2011) Expression and distribution of the sweet taste receptor isoforms T1R2 and T1R3 in human and rat bladders. J Urol 186(6):2455–2462. doi:10.1016/j.juro.2011.07.083

    Article  CAS  Google Scholar 

  54. Masubuchi Y, Nakagawa Y, Ma J, Sasaki T, Kitamura T, Yamamoto Y, Kurose H, Kojima I, Shibata H (2013) A novel regulatory function of sweet taste-sensing receptor in adipogenic differentiation of 3T3-L1 cells. PLoS One 8(1):e54500. doi:10.1371/journal.pone.0054500

    Article  CAS  Google Scholar 

  55. Simon BR, Parlee SD, Learman BS, Mori H, Scheller EL, Cawthorn WP, Ning X, Gallagher K, Tyrberg B, Assadi-Porter FM, Evans CR, MacDougald OA (2013) Artificial sweeteners stimulate adipogenesis and suppress lipolysis independently of sweet taste receptors. J Biol Chem 288(45):32475–32489. doi:10.1074/jbc.M113.514034

    Article  CAS  Google Scholar 

  56. Lund TC, Kobs AJ, Kramer A, Nyquist M, Kuroki MT, Osborn J, Lidke DS, Low-Nam ST, Blazar BR, Tolar J (2013) Bone marrow stromal and vascular smooth muscle cells have chemosensory capacity via bitter taste receptor expression. PLoS One 8(3):e58945. doi:10.1371/journal.pone.0058945

    Article  CAS  Google Scholar 

  57. Wauson EM, Zaganjor E, Lee AY, Guerra ML, Ghosh AB, Bookout AL, Chambers CP, Jivan A, McGlynn K, Hutchison MR, Deberardinis RJ, Cobb MH (2012) The G protein-coupled taste receptor T1R1/T1R3 regulates mTORC1 and autophagy. Mol Cell 47(6):851–862. doi:10.1016/j.molcel.2012.08.001

    Article  CAS  Google Scholar 

  58. Chaudhari N, Roper SD (2010) The cell biology of taste. J Cell Biol 190(3):285–296

    Article  CAS  Google Scholar 

  59. Chandrashekar J, Kuhn C, Oka Y, Yarmolinsky DA, Hummler E, Ryba NJ, Zuker CS (2010) The cells and peripheral representation of sodium taste in mice. Nature 464(7286):297–301

    Article  CAS  Google Scholar 

  60. Huang AL, Chen X, Hoon MA, Chandrashekar J, Guo W, Trankner D, Ryba NJ, Zuker CS (2006) The cells and logic for mammalian sour taste detection. Nature 442(7105):934–938

    Article  CAS  Google Scholar 

  61. Ishimaru Y, Inada H, Kubota M, Zhuang H, Tominaga M, Matsunami H (2006) Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor. Proc Natl Acad Sci U S A 103(33):12569–12574

    Article  CAS  Google Scholar 

  62. LopezJimenez ND, Cavenagh MM, Sainz E, Cruz-Ithier MA, Battey JF, Sullivan SL (2006) Two members of the TRPP family of ion channels, Pkd1l3 and Pkd2l1, are co-expressed in a subset of taste receptor cells. J Neurochem 98(1):68–77

    Article  CAS  Google Scholar 

  63. Horio N, Yoshida R, Yasumatsu K, Yanagawa Y, Ishimaru Y, Matsunami H, Ninomiya Y (2011) Sour taste responses in mice lacking PKD channels. PLoS One 6(5):e20007. doi:10.1371/journal.pone.0020007

    Article  CAS  Google Scholar 

  64. Bachmanov AA, Li X, Reed DR, Ohmen JD, Li S, Chen Z, Tordoff MG, de Jong PJ, Wu C, West DB, Chatterjee A, Ross DA, Beauchamp GK (2001) Positional cloning of the mouse saccharin preference (Sac) locus. Chem Senses 26(7):925–933

    Article  CAS  Google Scholar 

  65. Hoon MA, Adler E, Lindemeier J, Battey JF, Ryba NJ, Zuker CS (1999) Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity. Cell 96(4):541–551

    Article  CAS  Google Scholar 

  66. Kitagawa M, Kusakabe Y, Miura H, Ninomiya Y, Hino A (2001) Molecular genetic identification of a candidate receptor gene for sweet taste. Biochem Biophys Res Commun 283(1):236–242

    Article  CAS  Google Scholar 

  67. Max M, Shanker YG, Huang L, Rong M, Liu Z, Campagne F, Weinstein H, Damak S, Margolskee RF (2001) Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac. Nat Genet 28(1):58–63

    CAS  Google Scholar 

  68. Montmayeur JP, Liberles SD, Matsunami H, Buck LB (2001) A candidate taste receptor gene near a sweet taste locus. Nat Neurosci 4(5):492–498

    CAS  Google Scholar 

  69. Sainz E, Korley JN, Battey JF, Sullivan SL (2001) Identification of a novel member of the T1R family of putative taste receptors. J Neurochem 77(3):896–903

    Article  CAS  Google Scholar 

  70. Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E (2002) Human receptors for sweet and umami taste. Proc Natl Acad Sci U S A 99(7):4692–4696

    Article  CAS  Google Scholar 

  71. Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G, Ryba NJ, Zuker CS (2002) An amino-acid taste receptor. Nature 416(6877):199–202

    Article  CAS  Google Scholar 

  72. Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS (2000) A novel family of mammalian taste receptors. Cell 100(6):693–702

    Article  CAS  Google Scholar 

  73. Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, Guo W, Zuker CS, Ryba NJ (2000) T2Rs function as bitter taste receptors. Cell 100(6):703–711

    Article  CAS  Google Scholar 

  74. Matsunami H, Montmayeur JP, Buck LB (2000) A family of candidate taste receptors in human and mouse. Nature 404(6778):601–604

    Article  CAS  Google Scholar 

  75. Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K (2000) Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 407(6807):971–977. doi:10.1038/35039564

    Article  CAS  Google Scholar 

  76. Jones KA, Borowsky B, Tamm JA, Craig DA, Durkin MM, Dai M, Yao WJ, Johnson M, Gunwaldsen C, Huang LY, Tang C, Shen Q, Salon JA, Morse K, Laz T, Smith KE, Nagarathnam D, Noble SA, Branchek TA, Gerald C (1998) GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. Nature 396(6712):674–679. doi:10.1038/25348

    Article  CAS  Google Scholar 

  77. Kaupmann K, Malitschek B, Schuler V, Heid J, Froestl W, Beck P, Mosbacher J, Bischoff S, Kulik A, Shigemoto R, Karschin A, Bettler B (1998) GABA(B)-receptor subtypes assemble into functional heteromeric complexes. Nature 396(6712):683–687. doi:10.1038/25360

    Article  CAS  Google Scholar 

  78. Kuner R, Kohr G, Grunewald S, Eisenhardt G, Bach A, Kornau HC (1999) Role of heteromer formation in GABAB receptor function. Science 283(5398):74–77

    Article  CAS  Google Scholar 

  79. White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM, Marshall FH (1998) Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature 396(6712):679–682. doi:10.1038/25354

    Article  CAS  Google Scholar 

  80. Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS (2001) Mammalian sweet taste receptors. Cell 106(3):381–390

    Article  CAS  Google Scholar 

  81. Dong D, Jones G, Zhang S (2009) Dynamic evolution of bitter taste receptor genes in vertebrates. BMC Evol Biol 9:12

    Article  CAS  Google Scholar 

  82. Behrens M, Meyerhof W (2013) Bitter taste receptor research comes of age: from characterization to modulation of TAS2Rs. Semin Cell Dev Biol 24(3):215–221. doi:10.1016/j.semcdb.2012.08.006

    Article  CAS  Google Scholar 

  83. Meyerhof W, Batram C, Kuhn C, Brockhoff A, Chudoba E, Bufe B, Appendino G, Behrens M (2010) The molecular receptive ranges of human TAS2R bitter taste receptors. Chem Senses 35(2):157–170

    Article  CAS  Google Scholar 

  84. Chandrashekar J, Hoon MA, Ryba NJ, Zuker CS (2006) The receptors and cells for mammalian taste. Nature 444(7117):288–294

    Article  CAS  Google Scholar 

  85. Huang L, Shanker YG, Dubauskaite J, Zheng JZ, Yan W, Rosenzweig S, Spielman AI, Max M, Margolskee RF (1999) Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium. Nat Neurosci 2(12):1055–1062

    Article  CAS  Google Scholar 

  86. Rossler P, Boekhoff I, Tareilus E, Beck S, Breer H, Freitag J (2000) G protein betagamma complexes in circumvallate taste cells involved in bitter transduction. Chem Senses 25(4):413–421

    Article  CAS  Google Scholar 

  87. McLaughlin SK, McKinnon PJ, Margolskee RF (1992) Gustducin is a taste-cell-specific G protein closely related to the transducins. Nature 357(6379):563–569

    Article  CAS  Google Scholar 

  88. Rossler P, Kroner C, Freitag J, Noe J, Breer H (1998) Identification of a phospholipase C beta subtype in rat taste cells. Eur J Cell Biol 77(3):253–261

    Article  CAS  Google Scholar 

  89. Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ (2003) Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 112(3):293–301

    Article  CAS  Google Scholar 

  90. Clapp TR, Stone LM, Margolskee RF, Kinnamon SC (2001) Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction. BMC Neurosci 2:6

    Article  CAS  Google Scholar 

  91. Hisatsune C, Yasumatsu K, Takahashi-Iwanaga H, Ogawa N, Kuroda Y, Yoshida R, Ninomiya Y, Mikoshiba K (2007) Abnormal taste perception in mice lacking the type 3 inositol 1,4,5-trisphosphate receptor. J Biol Chem 282:37225–37231

    Article  CAS  Google Scholar 

  92. Miyoshi MA, Abe K, Emori Y (2001) IP(3) receptor type 3 and PLCbeta2 are co-expressed with taste receptors T1R and T2R in rat taste bud cells. Chem Senses 26(3):259–265

    Article  CAS  Google Scholar 

  93. Liu D, Liman ER (2003) Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proc Natl Acad Sci U S A 100(25):15160–15165

    Article  CAS  Google Scholar 

  94. Perez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H, Max M, Margolskee RF (2002) A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci 5(11):1169–1176

    Article  CAS  Google Scholar 

  95. Zhang Z, Zhao Z, Margolskee R, Liman E (2007) The transduction channel TRPM5 is gated by intracellular calcium in taste cells. J Neurosci 27(21):5777–5786

    Article  CAS  Google Scholar 

  96. Finger TE, Danilova V, Barrows J, Bartel DL, Vigers AJ, Stone L, Hellekant G, Kinnamon SC (2005) ATP signaling is crucial for communication from taste buds to gustatory nerves. Science 310(5753):1495–1499

    Article  CAS  Google Scholar 

  97. Huang YJ, Maruyama Y, Dvoryanchikov G, Pereira E, Chaudhari N, Roper SD (2007) The role of pannexin 1 hemichannels in ATP release and cell–cell communication in mouse taste buds. Proc Natl Acad Sci U S A 104(15):6436–6441

    Article  CAS  Google Scholar 

  98. Romanov RA, Rogachevskaja OA, Bystrova MF, Jiang P, Margolskee RF, Kolesnikov SS (2007) Afferent neurotransmission mediated by hemichannels in mammalian taste cells. EMBO J 26(3):657–667

    Article  CAS  Google Scholar 

  99. Taruno A, Vingtdeux V, Ohmoto M, Ma Z, Dvoryanchikov G, Li A, Adrien L, Zhao H, Leung S, Abernethy M, Koppel J, Davies P, Civan MM, Chaudhari N, Matsumoto I, Hellekant G, Tordoff MG, Marambaud P, Foskett JK (2013) CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature 495(7440):223–226. doi:10.1038/nature11906

    Article  CAS  Google Scholar 

  100. Cohen SP, Buckley BK, Kosloff M, Garland AL, Bosch DE, Cheng G Jr, Radhakrishna H, Brown MD, Willard FS, Arshavsky VY, Tarran R, Siderovski DP, Kimple AJ (2012) Regulator of G-protein signaling-21 (RGS21) is an inhibitor of bitter gustatory signaling found in lingual and airway epithelia. J Biol Chem 287(50):41706–41719. doi:10.1074/jbc.M112.423806

    Article  CAS  Google Scholar 

  101. von Buchholtz L, Elischer A, Tareilus E, Gouka R, Kaiser C, Breer H, Conzelmann S (2004) RGS21 is a novel regulator of G protein signalling selectively expressed in subpopulations of taste bud cells. Eur J Neurosci 19(6):1535–1544

    Article  Google Scholar 

  102. Hofer D, Puschel B, Drenckhahn D (1996) Taste receptor-like cells in the rat gut identified by expression of alpha-gustducin. Proc Natl Acad Sci U S A 93(13):6631–6634

    Article  CAS  Google Scholar 

  103. Ribatti D, Nico B, Crivellato E, Artico M (2006) Development of the blood-brain barrier: a historical point of view. Anat Rec B New Anat 289(1):3–8. doi:10.1002/ar.b.20087

    Article  Google Scholar 

  104. Benda P, Lightbody J, Sato G, Levine L, Sweet W (1968) Differentiated rat glial cell strain in tissue culture. Science 161(3839):370–371

    Article  CAS  Google Scholar 

  105. Pydi SP, Bhullar RP, Chelikani P (2012) Constitutively active mutant gives novel insights into the mechanism of bitter taste receptor activation. J Neurochem 122(3):537–544

    Article  CAS  Google Scholar 

  106. Hodges MR, Richerson GB (2010) Medullary serotonin neurons and their roles in central respiratory chemoreception. Respir Physiol Neurobiol 173(3):256–263. doi:10.1016/j.resp.2010.03.006

    Article  CAS  Google Scholar 

  107. Kidd M, Modlin IM, Gustafsson BI, Drozdov I, Hauso O, Pfragner R (2008) Luminal regulation of normal and neoplastic human EC cell serotonin release is mediated by bile salts, amines, tastants, and olfactants. Am J Physiol Gastrointest Liver Physiol 295(2):G260–G272

    Article  CAS  Google Scholar 

  108. Mace OJ, Lister N, Morgan E, Shepherd E, Affleck J, Helliwell P, Bronk JR, Kellett GL, Meredith D, Boyd R, Pieri M, Bailey PD, Pettcrew R, Foley D (2009) An energy supply network of nutrient absorption coordinated by calcium and T1R taste receptors in rat small intestine. J Physiol 587(Pt 1):195–210

    Article  CAS  Google Scholar 

  109. Swartz TD, Duca FA, de Wouters T, Sakar Y, Covasa M (2012) Up-regulation of intestinal type 1 taste receptor 3 and sodium glucose luminal transporter-1 expression and increased sucrose intake in mice lacking gut microbiota. Br J Nutr 107(5):621–630. doi:10.1017/S0007114511003412

    Article  CAS  Google Scholar 

  110. Young RL, Chia B, Isaacs NJ, Ma J, Khoo J, Wu T, Horowitz M, Rayner CK (2013) Disordered control of intestinal sweet taste receptor expression and glucose absorption in type 2 diabetes. Diabetes 62(10):3532–3541. doi:10.2337/db13-0581

    Article  CAS  Google Scholar 

  111. Haid D, Widmayer P, Breer H (2011) Nutrient sensing receptors in gastric endocrine cells. J Mol Histol 42(4):355–364. doi:10.1007/s10735-011-9339-1

    Article  CAS  Google Scholar 

  112. Hass N, Schwarzenbacher K, Breer H (2007) A cluster of gustducin-expressing cells in the mouse stomach associated with two distinct populations of enteroendocrine cells. Histochem Cell Biol 128(5):457–471

    Article  CAS  Google Scholar 

  113. Sothilingam V, Hass N, Breer H (2011) Candidate chemosensory cells in the stomach mucosa of young postnatal mice during the phases of dietary changes. Cell Tissue Res 344(2):239–249. doi:10.1007/s00441-011-1137-2

    Article  CAS  Google Scholar 

  114. Moran AW, Al-Rammahi MA, Arora DK, Batchelor DJ, Coulter EA, Daly K, Ionescu C, Bravo D, Shirazi-Beechey SP (2010) Expression of Na+/glucose co-transporter 1 (SGLT1) is enhanced by supplementation of the diet of weaning piglets with artificial sweeteners. Br J Nutr 104(5):637–646

    Article  CAS  Google Scholar 

  115. Widmayer P, Breer H, Hass N (2011) Candidate chemosensory cells in the porcine stomach. Histochem Cell Biol 136(1):37–45. doi:10.1007/s00418-011-0824-0

    Article  CAS  Google Scholar 

  116. Batchelor DJ, Al-Rammahi M, Moran AW, Brand JG, Li X, Haskins M, German AJ, Shirazi-Beechey SP (2011) Sodium/glucose cotransporter-1, sweet receptor, and disaccharidase expression in the intestine of the domestic dog and cat: two species of different dietary habit. Am J Physiol Regul Integr Comp Physiol 300(1):R67–R75. doi:10.1152/ajpregu.00262.2010

    Article  CAS  Google Scholar 

  117. Daly K, Al-Rammahi M, Arora DK, Moran AW, Proudman CJ, Ninomiya Y, Shirazi-Beechey SP (2012) Expression of sweet receptor components in equine small intestine: relevance to intestinal glucose transport. Am J Physiol Regul Integr Comp Physiol 303(2):R199–R208. doi:10.1152/ajpregu.00031.2012

    Article  CAS  Google Scholar 

  118. Taniguchi K (2004) Expression of the sweet receptor protein, T1R3, in the human liver and pancreas. J Vet Med Sci 66(11):1311–1314

    Article  CAS  Google Scholar 

  119. Hofer D, Drenckhahn D (1998) Identification of the taste cell G-protein, alpha-gustducin, in brush cells of the rat pancreatic duct system. Histochem Cell Biol 110(3):303–309

    Article  CAS  Google Scholar 

  120. Ruiz-Avila L, McLaughlin SK, Wildman D, McKinnon PJ, Robichon A, Spickofsky N, Margolskee RF (1995) Coupling of bitter receptor to phosphodiesterase through transducin in taste receptor cells. Nature 376(6535):80–85

    Article  CAS  Google Scholar 

  121. Hofer D, Asan E, Drenckhahn D (1999) Chemosensory perception in the gut. News Physiol Sci 14:18–23

    CAS  Google Scholar 

  122. Bezencon C, Furholz A, Raymond F, Mansourian R, Metairon S, Le Coutre J, Damak S (2008) Murine intestinal cells expressing Trpm5 are mostly brush cells and express markers of neuronal and inflammatory cells. J Comp Neurol 509(5):514–525. doi:10.1002/cne.21768

    Article  CAS  Google Scholar 

  123. Li Y, Kokrashvili Z, Mosinger B, Margolskee RF (2013) Gustducin couples fatty acid receptors to GLP-1 release in colon. Am J Physiol Endocrinol Metab 304(6):E651–E660. doi:10.1152/ajpendo.00471.2012

    Article  CAS  Google Scholar 

  124. Eberle JA, Richter P, Widmayer P, Chubanov V, Gudermann T, Breer H (2013) Band-like arrangement of taste-like sensory cells at the gastric groove: evidence for paracrine communication. Front Physiol 4:58. doi:10.3389/fphys.2013.00058

    Google Scholar 

  125. Kaske S, Krasteva G, Konig P, Kummer W, Hofmann T, Gudermann T, Chubanov V (2007) TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells. BMC Neurosci 8:49. doi:10.1186/1471-2202-8-49

    Article  CAS  Google Scholar 

  126. Kokrashvili Z, Rodriguez D, Yevshayeva V, Zhou H, Margolskee RF, Mosinger B (2009) Release of endogenous opioids from duodenal enteroendocrine cells requires Trpm5. Gastroenterology 137(2):598–606, 606 e591–592. doi:10.1053/j.gastro.2009.02.070

  127. Gerbe F, Legraverend C, Jay P (2012) The intestinal epithelium tuft cells: specification and function. Cell Mole Life Sci 69(17):2907–2917. doi:10.1007/s00018-012-0984-7

    Article  CAS  Google Scholar 

  128. Luciano L, Reale E, Ruska H (1968) On a glycogen containing brusc cell in the rectum of the rat. Z Zellforsch Mikrosk Anat 91(1):153–158

    Article  CAS  Google Scholar 

  129. Sternini C, Anselmi L, Rozengurt E (2008) Enteroendocrine cells: a site of ‘taste’ in gastrointestinal chemosensing. Curr Opin Endocrinol Diabetes Obes 15(1):73–78

    Article  CAS  Google Scholar 

  130. Le Neve B, Foltz M, Daniel H, Gouka R (2010) The steroid glycoside H.g.-12 from Hoodia gordonii activates the human bitter receptor TAS2R14 and induces CCK release from HuTu-80 cells. Am J Physiol Gastrointest Liver Physiol 299:G1368–G1375

    Article  CAS  Google Scholar 

  131. McIntyre N, Holdsworth CD, Turner DS (1964) New interpretation of oral glucose tolerance. Lancet 2(7349):20–21

    Article  CAS  Google Scholar 

  132. Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132(6):2131–2157. doi:10.1053/j.gastro.2007.03.054

    Article  CAS  Google Scholar 

  133. Sato S, Hokari R, Kurihara C, Sato H, Narimatsu K, Hozumi H, Ueda T, Higashiyama M, Okada Y, Watanabe C, Komoto S, Tomita K, Kawaguchi A, Nagao S, Miura S (2013) Dietary lipids and sweeteners regulate glucagon-like peptide-2 secretion. Am J Physiol Gastrointest Liver Physiol 304(8):G708–G714. doi:10.1152/ajpgi.00282.2012

    Article  CAS  Google Scholar 

  134. Gerspach AC, Steinert RE, Schonenberger L, Graber-Maier A, Beglinger C (2011) The role of the gut sweet taste receptor in regulating GLP-1, PYY, and CCK release in humans. Am J Physiol Endocrinol Metab 301(2):E317–E325. doi:10.1152/ajpendo.00077.2011

    Article  CAS  Google Scholar 

  135. Ford HE, Peters V, Martin NM, Sleeth ML, Ghatei MA, Frost GS, Bloom SR (2011) Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects. Eur J Clin Nutr 65:508–513

    Article  CAS  Google Scholar 

  136. Fujita Y, Wideman RD, Speck M, Asadi A, King DS, Webber TD, Haneda M, Kieffer TJ (2009) Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo. Am J Physiol Endocrinol Metab 296(3):E473–E479

    Article  CAS  Google Scholar 

  137. Ma J, Bellon M, Wishart JM, Young R, Blackshaw LA, Jones KL, Horowitz M, Rayner CK (2009) Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects. Am J Physiol Gastrointest Liver Physiol 296(4):G735–G739

    Article  CAS  Google Scholar 

  138. Nakagawa Y, Nagasawa M, Mogami H, Lohse M, Ninomiya Y, Kojima I (2013) Multimodal function of the sweet taste receptor expressed in pancreatic beta-cells: generation of diverse patterns of intracellular signals by sweet agonists. Endocr J 60(10):1191–1206

    Article  CAS  Google Scholar 

  139. Nakagawa Y, Ohtsu Y, Nagasawa M, Shibata H, Kojima I (2014) Glucose promotes its own metabolism by acting on the cell-surface glucose-sensing receptor T1R3. Endocr J 61:119–131

    Article  CAS  Google Scholar 

  140. Zhao GQ, Zhang Y, Hoon MA, Chandrashekar J, Erlenbach I, Ryba NJ, Zuker CS (2003) The receptors for mammalian sweet and umami taste. Cell 115(3):255–266

    Article  CAS  Google Scholar 

  141. Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger MA, Lytton J, Hebert SC (1993) Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature 366(6455):575–580. doi:10.1038/366575a0

    Article  CAS  Google Scholar 

  142. Wellendorph P, Brauner-Osborne H (2004) Molecular cloning, expression, and sequence analysis of GPRC6A, a novel family C G-protein-coupled receptor. Gene 335:37–46. doi:10.1016/j.gene.2004.03.003

    Article  CAS  Google Scholar 

  143. Wellendorph P, Hansen KB, Balsgaard A, Greenwood JR, Egebjerg J, Brauner-Osborne H (2005) Deorphanization of GPRC6A: a promiscuous l-alpha-amino acid receptor with preference for basic amino acids. Mol Pharmacol 67(3):589–597. doi:10.1124/mol.104.007559

    Article  CAS  Google Scholar 

  144. Torres N, Noriega L, Tovar AR (2009) Nutrient modulation of insulin secretion. Vitam Horm 80:217–244. doi:10.1016/S0083-6729(08)00609-2

    Article  CAS  Google Scholar 

  145. Imoto T, Miyasaka A, Ishima R, Akasaka K (1991) A novel peptide isolated from the leaves of Gymnema sylvestre–I. Characterization and its suppressive effect on the neural responses to sweet taste stimuli in the rat. Comp Biochem Physiol A Comp Physiol 100(2):309–314

    Article  CAS  Google Scholar 

  146. Ninomiya Y, Imoto T (1995) Gurmarin inhibition of sweet taste responses in mice. Am J Physiol 268(4 Pt 2):R1019–R1025

    CAS  Google Scholar 

  147. Ninomiya Y, Nakashima K, Fukuda A, Nishino H, Sugimura T, Hino A, Danilova V, Hellekant G (2000) Responses to umami substances in taste bud cells innervated by the chorda tympani and glossopharyngeal nerves. J Nutr 130(4S Suppl):950S–953S

    CAS  Google Scholar 

  148. Yamamoto T, Matsuo R, Fujimoto Y, Fukunaga I, Miyasaka A, Imoto T (1991) Electrophysiological and behavioral studies on the taste of umami substances in the rat. Physiol Behav 49(5):919–925

    Article  CAS  Google Scholar 

  149. Nakamura E, Hasumura M, San Gabriel A, Uneyama H, Torii K (2010) New frontiers in gut nutrient sensor research: luminal glutamate-sensing cells in rat gastric mucosa. J Pharmacol Sci 112(1):13–18

    Article  CAS  Google Scholar 

  150. Straub SG, Mulvaney-Musa J, Yajima H, Weiland GA, Sharp GW (2003) Stimulation of insulin secretion by denatonium, one of the most bitter-tasting substances known. Diabetes 52(2):356–364

    Article  CAS  Google Scholar 

  151. Behrens M, Meyerhof W (2010) Oral and extraoral bitter taste receptors. In: Meyerhof W, Beisiegel U, Joost H-G (eds) Sensory and metabolic control of energy balance, vol 52. Results and problems in cell differentiation. Springer, Heidelberg, pp 87-99. doi:10.1007/978-3-642-14426-4_8

  152. Little TJ, Gupta N, Case RM, Thompson DG, McLaughlin JT (2009) Sweetness and bitterness taste of meals per se does not mediate gastric emptying in humans. Am J Physiol Regul Integr Comp Physiol 297(3):R632–R639

    Article  CAS  Google Scholar 

  153. Wicks D, Wright J, Rayment P, Spiller R (2005) Impact of bitter taste on gastric motility. Eur J Gastroenterol Hepatol 17(9):961–965

    Article  Google Scholar 

  154. Jeon TI, Seo YK, Osborne TF (2011) Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving CCK. Biochem J 438(1):33–37

    Article  CAS  Google Scholar 

  155. Hao S, Dulake M, Espero E, Sternini C, Raybould HE, Rinaman L (2009) Central Fos expression and conditioned flavor avoidance in rats following intragastric administration of bitter taste receptor ligands. Am J Physiol Regul Integr Comp Physiol 296(3):R528–R536

    Article  CAS  Google Scholar 

  156. Sbarbati A, Tizzano M, Merigo F, Benati D, Nicolato E, Boschi F, Cecchini MP, Scambi I, Osculati F (2009) Acyl homoserine lactones induce early response in the airway. Anat Rec 292(3):439–448. doi:10.1002/ar.20866

    Article  Google Scholar 

  157. Barham HP, Cooper SE, Anderson CB, Tizzano M, Kingdom TT, Finger TE, Kinnamon SC, Ramakrishnan VR (2013) Solitary chemosensory cells and bitter taste receptor signaling in human sinonasal mucosa. Int Forum Allergy Rhinol 3(6):450–457. doi:10.1002/alr.21149

    Article  Google Scholar 

  158. Lee RJ, Chen B, Redding KM, Margolskee RF, Cohen NA (2013) Mouse nasal epithelial innate immune responses to Pseudomonas aeruginosa quorum-sensing molecules require taste signaling components. Innate Immun. doi:10.1177/1753425913503386

    Google Scholar 

  159. Belvisi MG, Dale N, Birrell MA, Canning BJ (2011) Bronchodilator activity of bitter tastants in human tissue. Nat Med 17(7):776. doi:10.1038/nm0711-776a, author reply 776–778

    Article  CAS  Google Scholar 

  160. Morice AH, Bennett RT, Chaudhry MA, Cowen ME, Griffin SC, Loubani M (2011) Effect of bitter tastants on human bronchi. Nat Med 17(7):775. doi:10.1038/nm0711-775

    Article  CAS  Google Scholar 

  161. Behrens M, Brockhoff A, Kuhn C, Bufe B, Winnig M, Meyerhof W (2004) The human taste receptor hTAS2R14 responds to a variety of different bitter compounds. Biochem Biophys Res Commun 319(2):479–485

    Article  CAS  Google Scholar 

  162. Levit A, Nowak S, Peters M, Wiener A, Meyerhof W, Behrens M, Niv MY (2013) The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14. FASEB J. doi:10.1096/fj.13-242594

    Google Scholar 

  163. Zhou PZ, Babcock J, Liu LQ, Li M, Gao ZB (2011) Activation of human ether-a-go-go related gene (hERG) potassium channels by small molecules. Acta Pharmacol Sin 32(6):781–788. doi:10.1038/aps.2011.70

    Article  CAS  Google Scholar 

  164. Yoshida M, Yoshida K (2011) Sperm chemotaxis and regulation of flagellar movement by Ca2+. Mol Hum Reprod 17(8):457–465. doi:10.1093/molehr/gar041

    Article  CAS  Google Scholar 

  165. Kaupp UB, Kashikar ND, Weyand I (2008) Mechanisms of sperm chemotaxis. Annu Rev Physiol 70:93–117. doi:10.1146/annurev.physiol.70.113006.100654

    Article  CAS  Google Scholar 

  166. Behrens M, Bartelt J, Reichling C, Winnig M, Kuhn C, Meyerhof W (2006) Members of RTP and REEP gene families influence functional bitter taste receptor expression. J Biol Chem 281(29):20650–20659

    Article  CAS  Google Scholar 

  167. Fehr J, Meyer D, Widmayer P, Borth HC, Ackermann F, Wilhelm B, Gudermann T, Boekhoff I (2007) Expression of the G-protein alpha-subunit gustducin in mammalian spermatozoa. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 193(1):21–34

    Article  CAS  Google Scholar 

  168. Li X, Li W, Wang H, Cao J, Maehashi K, Huang L, Bachmanov AA, Reed DR, Legrand-Defretin V, Beauchamp GK, Brand JG (2005) Pseudogenization of a sweet-receptor gene accounts for cats’ indifference toward sugar. PLoS Genet 1(1):27–35

    Article  CAS  Google Scholar 

  169. Shi P, Zhang J (2006) Contrasting modes of evolution between vertebrate sweet/umami receptor genes and bitter receptor genes. Mol Biol Evol 23(2):292–300

    Article  CAS  Google Scholar 

  170. Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B, Bai Y, Zhang Z, Zhang Y, Wang W, Li J, Wei F, Li H, Jian M, Li J, Zhang Z, Nielsen R, Li D, Gu W, Yang Z, Xuan Z, Ryder OA, Leung FC, Zhou Y, Cao J, Sun X, Fu Y, Fang X, Guo X, Wang B, Hou R, Shen F, Mu B, Ni P, Lin R, Qian W, Wang G, Yu C, Nie W, Wang J, Wu Z, Liang H, Min J, Wu Q, Cheng S, Ruan J, Wang M, Shi Z, Wen M, Liu B, Ren X, Zheng H, Dong D, Cook K, Shan G, Zhang H, Kosiol C, Xie X, Lu Z, Zheng H, Li Y, Steiner CC, Lam TT, Lin S, Zhang Q, Li G, Tian J, Gong T, Liu H, Zhang D, Fang L, Ye C, Zhang J, Hu W, Xu A, Ren Y, Zhang G, Bruford MW, Li Q, Ma L, Guo Y, An N, Hu Y, Zheng Y, Shi Y, Li Z, Liu Q, Chen Y, Zhao J, Qu N, Zhao S, Tian F, Wang X, Wang H, Xu L, Liu X, Vinar T, Wang Y, Lam TW, Yiu SM, Liu S, Zhang H, Li D, Huang Y, Wang X, Yang G, Jiang Z, Wang J, Qin N, Li L, Li J, Bolund L, Kristiansen K, Wong GK, Olson M, Zhang X, Li S, Yang H, Wang J, Wang J (2010) The sequence and de novo assembly of the giant panda genome. Nature 463(7279):311–317. doi:10.1038/nature08696

    Article  CAS  Google Scholar 

  171. Jiang P, Josue J, Li X, Glaser D, Li W, Brand JG, Margolskee RF, Reed DR, Beauchamp GK (2012) Major taste loss in carnivorous mammals. Proc Natl Acad Sci U S A 109(13):4956–4961

    Article  CAS  Google Scholar 

  172. Zhao H, Xu D, Zhang S, Zhang J (2012) Genomic and genetic evidence for the loss of umami taste in bats. Genome Biol Evol 4(1):73–79. doi:10.1093/gbe/evr126

    Article  CAS  Google Scholar 

  173. Zhao H, Zhou Y, Pinto CM, Charles-Dominique P, Galindo-Gonzalez J, Zhang S, Zhang J (2010) Evolution of the sweet taste receptor gene Tas1r2 in bats. Mol Biol Evol 27(11):2642–2650. doi:10.1093/molbev/msq152

    Article  CAS  Google Scholar 

  174. Dunn-Meynell AA, Sanders NM, Compton D, Becker TC, Eiki J, Zhang BB, Levin BE (2009) Relationship among brain and blood glucose levels and spontaneous and glucoprivic feeding. J Neurosci 29(21):7015–7022. doi:10.1523/JNEUROSCI.0334-09.2009

    Article  CAS  Google Scholar 

  175. Behrens M, Born S, Redel U, Voigt N, Schuh V, Raguse JD, Meyerhof W (2012) Immunohistochemical detection of TAS2R38 protein in human taste cells. PLoS One 7(7):e40304

    Article  CAS  Google Scholar 

  176. Clark AA, Liggett SB, Munger SD (2012) Extraoral bitter taste receptors as mediators of off-target drug effects. FASEB J 26(12):4827–4831. doi:10.1096/fj.12-215087

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the German Ministry of Education and Research (BMBF, #0315669, to WM and MB) for financial support.

Author information

Authors and Affiliations

  1. Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany

    Maik Behrens, Simone Prandi & Wolfgang Meyerhof

Authors
  1. Maik Behrens
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Simone Prandi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wolfgang Meyerhof
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maik Behrens .

Editor information

Editors and Affiliations

  1. Deutsche Forschungsanstalt fuer Lebensmittelchemie, Leibniz Institut, Freising, Germany

    Dietmar Krautwurst

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Behrens, M., Prandi, S., Meyerhof, W. (2014). Taste Receptor Gene Expression Outside the Gustatory System. In: Krautwurst, D. (eds) Taste and Smell. Topics in Medicinal Chemistry, vol 23. Springer, Cham. https://doi.org/10.1007/7355_2014_79

Download citation

Publish with us

Policies and ethics

Search

Navigation